Kinetically regulated one-pot synthesis of cationic gold nanoparticles and their size-dependent antibacterial mechanism

Cationic gold nanoparticles (cAuNPs) have been regarded as promising candidates for antibacterial applications due to their high surface charge density, favorable biocompatibility, and controllable surface chemistry. Nevertheless, the complicated fabrication process and unclear antibacterial mechanism have greatly hindered the further biomedical application of cAuNPs. Herein, we have developed a simple and controllable strategy for synthesizing cAuNPs with tailored size and antibacterial behavior by kinetically modulating the reaction process. Specifically, a functional ligand, (11-mercaptoundecyl)-N, N, N-trimethylammonium bromide (MUTAB), was chosen to chemically manipulate the positive surface charge of cAuNPs via a one-step strategy. The size of cAuNPs could be flexibly adjusted from 1.1 to 14.8 nm by simply elevating the stirring speed of the reaction from 0 to 1500 rpm. Further studies revealed that the antibacterial effect of cAuNPs was strongly correlated with the particle size. MUTAB-protected ultrasmall gold nanoclusters (MUTAB-AuNCs) were able to eradicate E. coli at a concentration as low as 1.25 μg mL^–1, while the minimum inhibitory concentration of MUTAB-AuNPs with a large size for E. coli was 5 μg mL^–1. Mechanistic investigation revealed that MUTAB-AuNPs were able to damage the bacterial membrane and stimulate the production of reactive oxygen species more effectively than MUTAB-AuNCs. Conversely, MUTAB-AuNCs were more active in inducing membrane depolarization in contrast to MUTAB-AuNPs, suggesting the unique size-dependent antibacterial manner of cAuNPs. This study presents a new strategy for the controlled preparation of cAuNPs with distinct sizes and antibacterial behavior, laying a valuable foundation for developing efficient cationic NP-based bactericidal agents.